Project Summary/Abstract: Novelty/sensation seeking as a construct in human personality inventories has been extensively associated with drug use. Novelty and sensation seeking have also been associated with elevated drug intake in rodent populations, suggesting an overlap in the neural substrates that encode the reinforcing values of both of these constructs. Further examination of novel stimuli has also supported the relationship with drugs of abuse. Novel stimuli can increase mesolimbic dopamine (DA) activity and produce reinforced behavior in rodents, suggesting that the study of novelty/sensation seeking can provide insight into processes related to addiction. Preliminary data in this proposal demonstrates that dynamic visual stimuli are reinforcing in mice, as they will perform an operant response to obtain it (a task we have termed operant sensation seeking (OSS)). Additionally, they exhibit persistent operant behavior when the stimuli are taken away, a phenomenon common to operant studies using drugs of abuse. Acute and long-term effects of OSS relative to food and cocaine will be characterized using immunohistochemistry and electrophysiology. These experiments will provide insight into how natural and drug reinforcers are encoded in the brain. The role of the glutamate mGluR5 receptor in OSS will be examined using novel pharmacological and genetic tools. This receptor is involved in mediating the reinforcing effects of drug abuse and may be important in OSS as well. Finally, the influence of genetics on OSS will be assessed by screening recombinant inbred strains of mice (BXDs) that are divergent in limbic structure, stress responsivity, and exploratory behavior. These data will reveal the contributions of genetic factors that underlie reinforcement and persistent seeking behavior following removal of OSS stimuli. Understanding how genetics can contribute to these behaviors may improve our knowledge of which people are especially at risk for addiction.